This research paper was presented at
the National Stroke Association Conference in Boston, October 16-18, 1997.

Oxygen is Mother Nature's most
natural drug, most important nutrient and the element most essential to life.
Hyperbaric oxygen therapy is a unique and important treatment which uses oxygen
under pressure for the correction and healing of stroke and traumatically brain
injured (TBI) individuals. The first clinical use of hyperbaric oxygen for the
treatment of stroke patients was reported in 1965 and many studies have been
done since then proving its safety and effectiveness.1,2

Most people believe that a stroke is
due to the death of brain cells. Brain cells are thought to die as a direct
result of the interruption of blood flow and the resulting lack of oxygen to a
part of the brain. This concept of what a stroke is has been dogma for at least
the last 100 years. This traditional concept of infarction, that the brain
tissue dies from a blood and oxygen shortage lasting more than a few minutes,
is no longer valid.1 A different concept has been slowly evolving over the past
25 years that the death of brain cells occurs only when the flow of blood falls
below a certain level (approximately 8-10 ml/100 gr./min.) while at slightly
higher levels the tissue remains alive but not able to function. Thus in the
acute stroke the affected central core brain tissue may die while the more
peripheral tissues remain alive for many years after the initial insult,
depending on the amount of blood the brain tissue receives.

Those brain areas that are injured
and are not receiving enough blood flow as a result of the stroke or trauma are
now referred to as the "ischemic penumbra." This is the area that
surrounds the central core of infarcted (dead) tissue. These "rim"
tissues do not receive enough oxygen to function but do receive enough to stay
alive. These brain cells have been described as "sleeping beauties,"
"sleeping neurons," or "dormant" or "idling
neurons." These neurons are nonfunctional but anatomically intact and can
be revived. When I describe this phenomena to my patients, I explain that some
of the brain cells are sick and just like we do when we are sick, we want to
lie down and not do anything. You also tend to be more grumpy, tired and
irritable than otherwise. These sick brain cells often are responsible for the
stroke or TBI patient being grumpy, irritable, fatigued, depressed, etc.
because cells in the emotional and cognitive areas of the brain are not
functioning effectively.

In the acute case as much as 85% of
the brain injury involves those tissues that surround the central core of dead
brain tissue. It is this ischemic penumbral tissue that the newly approved
"clot busting" drugs (tPA-tissue plasminogen activator) help to save
if they are given within the first three hours of the onset of a blood clot
type of stroke. Hyperbaric oxygen is being considered as a treatment in
conjunction with tPA in the acute stroke setting since it will extend the
period of time during which the tPA can be given.

A fundamental aspect of the
pathology of chronic stroke and TBI patients is that damaged blood vessels are
the cause of the ischemic penumbra. Unfortunately the brain has only limited
healing properties and these seem to run their course during the first year
after the traumatic brain injury. During this first year a number of healing
processes are occurring. A major damaging process that occurs in the acute stroke
or TBI is edema (swelling of the tissues as a result of the damage). This
swelling may take up to 9 to 12 months to resolve and during this time the
swelling will be compressing brain blood vessels Ð limiting the flow of blood
to the damaged tissues. As the swelling goes away, some of the blood vessels
will regain their original diameters and normal blood flow will resume.

Another process that occurs during
this first year is "neovascularization," also known as
"angiogenesis." This is the process of forming new capillaries which
extend from the surrounding healthy brain tissue into the areas of the ischemic
penumbra. The outermost portions of the ischemic penumbra (those portions
closest to normal brain tissue) are able to metabolize slightly since they are
receiving more blood than the more centrally located ischemic tissues. This
metabolism releases a breakdown product of ATP called adenosine. Adenosine is
released from ischemic tissues when ATP is being utilized by the cell for
repair processes. Adenosine is a vasodilator and also stimulates new
capillaries to grow into the ischemic penumbra (neovascularization). Thus
during the first year after a stroke or TBI, new blood vessels are stimulated
to move into the ischemic penumbra to re-supply it with a new blood supply.

Unfortunately, the ischemic
penumbral tissues closer to the infarct area usually are not receiving enough
oxygen or nutrients to generate ATP Ð either from aerobic or anaerobic
metabolism. Due to the lack of ATP formation, adenosine is not produced and the
formation of new capillaries does not occur. Thus the ischemic penumbra remains
ischemic because the process of neovascularization is not able to be completed.
This often results in a substantial amount of brain tissue that remains ischemic
and non-functioning in the chronic stroke and TBI patient's brain. This failure
of natural healing processes is due ultimately to damaged blood vessels and
their inability to provide oxygen and nutrients to those portions of the brain
that are damaged.

Hyperbaric oxygen works to improve
stroke and TBI patients by repairing and generating new blood vessels to the
injured parts of the brain. Once the ischemic tissues no longer suffer from a
lack of oxygen, they are able to begin to repair the injured neurons, glial
cells and extracellular matrix. The generation of new blood vessels occurs as a
direct result of daily hyperbaric oxygen treatments. This does not occur with
pure oxygen at normal atmospheric pressures. The number of treatments required
varies for each individual but in my experience the best results occur when at
least 60 daily treatments are done. If only 20 to 30 treatments are done, the
patient will often experience "backsliding" and may lose some of the
improvement they gained from the hyperbaric oxygen treatments. In addition,
some patients will not even begin to improve until they have had more than 30
or 40 treatments.

Hyperbaric oxygen therapy feels much
like going for a ride in a modern day jet Ð the chamber even looks like the
cockpit of a jet fighter plane! As you start your treatment you are sitting
upright at a comfortable angle inside of this cockpit-like chamber. You have an
oxygen mask over your mouth and nose, the door is shut and you feel a slight
movement of air as the chamber begins to be filled with more air. As the air
enters the chamber you may notice a slight discomfort in one or both ears just
like you have experienced while flying in the large commercial jets. You may
choose to swallow, chew gum or hold your nose and blow outward to help equalize
the pressure in your ears. We have seen three patients out of more than 500 who
have had enough pain and discomfort in clearing their ears that we have had to
send them to the ear specialist for a simple insertion of a small tube through
the ear drum. In these cases, this cured the problem so the person was able to
continue with the program without further pain and with no problems with their
hearing.

Severe, advanced emphysema may be a
contraindication if the person has large lung bullae (large air filled sacks
within the lung). The bullae may trap the oxygen and rupture while the person
is decompressing. The presence of large bullae can be checked by ordering a CT
exam of the chest.

Patients who have had a seizure
worry about having another episode while in the chamber. K.K. Jain1 the MD
neurosurgeon who wrote the Textbook of Hyperbaric Medicine states,
"Seizures are extremely rare and no more than a chance occurrence during
HBO sessions at pressures between 1.5 and 2 ATA even in patients with a history
of epilepsy." Our experience is similar.

Claustrophobia is an often voiced
fear but once the person begins to work with our technicians, he or she is
generally able to overcome their fears without a problem.

Muscle, bone and peripheral nerve
dysfunction and atrophy are also major factors that are present in many
patients. This is due to inactivity, loss of weight bearing, hormonal
deficiencies, mineral deficiencies and a variety of different disease states.
These dysfunctions and atrophy require aggressive, daily rehabilitative efforts
for a minimum of two months to produce significant, long term beneficial
results.

From a practical point of view, the
patient who is being considered for hyperbaric oxygen therapy can be tested to
determine if he/she is a candidate. A 3-D SPECT scan (single photon
computerized tomogram) for determining cerebral blood flow is available at most
larger hospitals in the USA. If this test is done and shows diminished brain
blood flow, the patient has a good chance for significant improvement with a
course of hyperbaric oxygen treatments.

The treatments are usually 90
minutes each day for 60 days. In my experience, this protocol produces the best
overall results when the therapy is given in combination with other treatments
such as physical, occupational and biofeedback therapy. Our average patient
comes to us 2-1/2 years after their stroke or TBI. They usually have gone
through all of the standard therapies and have not improved over the past year
despite continuing physical therapy and an active exercise program. They or
their family members recognize their lack of improvement and come to us as
"the last hope." Due to the severity of their disabilities and their
failure to improve with conventional therapies, most patients hope that the use
of hyperbaric oxygen will produce gratifying results. However, even with 60
days of hyperbaric oxygen treatments, the results may not reach their
expectations, especially if only hyperbaric oxygen is used. Most every patient
we see would like to maximize their chances of improving while they are
attending our clinic. In view of their desires and the fact that the
combination of hyperbaric oxygen and other therapies produces improved overall
results, we offer daily physical, occupational, speech, vision, biofeedback,
nutritional, vitamin, hormonal and growth factor therapies to help our patients
reach their maximum recovery potential.

In addition to the use of the above
mentioned therapies I have also found that many patients have other disease
processes which must be treated to maximize their recovery. Many patients when
entering our program suffer from chronic urinary tract or other infections,
have autoimmune disorders such as vasculitis, suffer from diabetes and diabetic
neuropathy, have osteoporosis of the paralyzed limb(s), have serious
atherosclerosis or have hormonal deficiencies. All of these conditions and
problems must be addressed to help maximize the patient's healing.

Results of Fifty Cases:

Fifty stable and no longer improving
stroke patients (average age 62 years) with an average time of 28 months since
their stroke received hyperbaric oxygen therapy for 90 minutes each day, 6 days
a week for 60 treatments, as well as physical therapy for 2 hours and EEG
Biofeedback for 30 minutes each day, 5 days a week. Physical therapist's
evaluations and patient's questionnaires were collected prior to and after the
program.

Results from patients'
questionnaires showed that 95.83% of the patients or their family members
believed that the patient experienced one or more improvements in their motor
ability, sensitivity to touch and temperature, bladder and bowel control,
cognition, memory, speech, sight and hearing. At the conclusion of the program,
29% of the patients ranked the program as good, 42% of the patients ranked it
as excellent, and 25% reported that this program was stupendous.

The physical therapist's evaluation
included range of motion, extremity's strength, bed mobility, bed to chair
transfers and body's balance level. By the therapist's evaluations, 100% of the
patients showed improvements in one or more functions. Of those, 18% had a mild
gain, 48% received a good gain, and 34% an excellent gain.

No side effects or problems were
encountered with the combination of therapies for treating chronic stroke
patients.

Hyperbaric oxygen therapy in Thai autistic children.

Abstract

BACKGROUND:
Autism is a developmental and behavioral pattern, the triad of impairments, 1.
social interaction, 2. social communication, 3. imagination. Their memories are
seemingly in picture or photo records. Difficulties in the treatment,
management, and handling of autistic children are the main problems. Hyperbaric
oxygen therapy (HBOT) is a modern treatment in Thailand for nitrogen imbalance
(Decompression sickness syndrome or Caisson disease). HBOT can increase plasma
oxygen to the tissues including the brain. OBJECTIVE: To determine whether
Hyperbaric Oxygen Therapy is safe to use in children with autism, and has a
statistically significant effect on autistic symptoms. This is the first study
in Thailand.
MATERIAL AND METHOD: Thai Autistic children (n = 7) received HBOT (1.3 atm., 10
sessions) treatment. Assessment was done before and after treatment in five
domains: Social development, Fine motor and Eye-hand coordination, Language
development, Gross motor development, Self-help skills. RESULTS: Improvement
was shown in five domains with a significant level. Seventy-five percent of
children shown improvement while 25% did not seem to respond to the treatment.
CONCLUSION: HBOT is a new treatment for Thai autistic children. Many scientific
studies recently have shown that HBOT could be an effective treatment for
autistic children. It could improve the major autistic symptoms.

Hyperbaric oxygen therapy may improve symptoms in autistic
children.

Abstract

Autism
is a neurodevelopmental disorder that currently affects as many as 1 out of 166
children in the United
States. Recent research has discovered that
some autistic individuals have decreased cerebral perfusion, evidence of
neuroinflammation, and increased markers of oxidative stress. Multiple
independent single photon emission computed tomography (SPECT) and positron
emission tomography (PET) research studies have revealed hypoperfusion to
several areas of the autistic brain, most notably the temporal regions and
areas specifically related to language comprehension and auditory processing.
Several studies show that diminished blood flow to these areas correlates with
many of the clinical features associated with autism including repetitive,
self-stimulatory and stereotypical behaviors, and impairments in communication,
sensory perception, and social interaction. Hyperbaric oxygen therapy (HBOT)
has been used with clinical success in several cerebral hypoperfusion syndromes
including cerebral palsy, fetal alcohol syndrome, closed head injury, and
stroke. HBOT can compensate for decreased blood flow by increasing the oxygen
content of plasma and body tissues and can even normalize oxygen levels in
ischemic tissue. In addition, animal studies have shown that HBOT has potent
anti-inflammatory effects and reduces oxidative stress. Furthermore, recent
evidence demonstrates that HBOT mobilizes stem cells from human bone marrow,
which may aid recovery in neurodegenerative diseases. Based upon these
findings, it is hypothesized that HBOT will improve symptoms in autistic
individuals. A retrospective case series is presented that supports this
hypothesis.

The effects of hyperbaric oxygen therapy on oxidative stress,
inflammation, and symptoms in children with autism: an open-label pilot study.

Abstract

BACKGROUND:
Recently, hyperbaric oxygen therapy (HBOT) has increased in popularity as a
treatment for autism. Numerous studies document oxidative stress and
inflammation in individuals with autism; both of these conditions have
demonstrated improvement with HBOT, along with enhancement of neurological
function and cognitive performance. In this study, children with autism were
treated with HBOT at atmospheric pressures and oxygen concentrations in current
use for this condition. Changes in markers of oxidative stress and inflammation
were measured. The children were evaluated to determine clinical effects and
safety. METHODS: Eighteen children with autism, ages 3-16 years, underwent 40
hyperbaric sessions of 45 minutes duration each at either 1.5 atmospheres (atm)
and 100% oxygen, or at 1.3 atm and 24% oxygen. Measurements of C-reactive
protein (CRP) and markers of oxidative stress, including plasma oxidized
glutathione (GSSG), were assessed by fasting blood draws collected before and
after the 40 treatments. Changes in clinical symptoms, as rated by parents,
were also assessed. The children were closely monitored for potential adverse
effects. RESULTS: At the endpoint of 40 hyperbaric sessions, neither group
demonstrated statistically significant changes in mean plasma GSSG levels,
indicating intracellular oxidative stress appears unaffected by either regimen.
A trend towards improvement in mean CRP was present in both groups; the largest
improvements were observed in children with initially higher elevations in CRP.
When all 18 children were pooled, a significant improvement in CRP was found (p
= 0.021). Pre- and post-parental observations indicated statistically
significant improvements in both groups, including motivation, speech, and
cognitive awareness (p < 0.05). No major adverse events were observed.
CONCLUSION: In this prospective pilot study of children with autism, HBOT at a
maximum pressure of 1.5 atm with up to 100% oxygen was safe and well tolerated.
HBOT did not appreciably worsen oxidative stress and significantly decreased
inflammation as measured by CRP levels. Parental observations support anecdotal
accounts of improvement in several domains of autism. However, since this was
an open-label study, definitive statements regarding the efficacy of HBOT for
the treatment of individuals with autism must await results from double-blind,
controlled trials. TRIAL REGISTRATION: clinicaltrials.gov NCT00324909.

Abstract

BACKGROUND:
Several uncontrolled studies of hyperbaric treatment in children with autism
have reported clinical improvements; however, this treatment has not been
evaluated to date with a controlled study. We performed a multicenter,
randomized, double-blind, controlled trial to assess the efficacy of hyperbaric
treatment in children with autism. METHODS: 62 children with autism recruited
from 6 centers, ages 2-7 years (mean 4.92 +/- 1.21), were randomly assigned to
40 hourly treatments of either hyperbaric treatment at 1.3 atmosphere (atm) and
24% oxygen ("treatment group", n = 33) or slightly pressurized room
air at 1.03 atm and 21% oxygen ("control group", n = 29). Outcome
measures included Clinical Global Impression (CGI) scale, Aberrant Behavior
Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC). RESULTS:
After 40 sessions, mean physician CGI scores significantly improved in the
treatment group compared to controls in overall functioning (p = 0.0008),
receptive language (p < 0.0001), social interaction (p = 0.0473), and eye
contact (p = 0.0102); 9/30 children (30%) in the treatment group were rated as "very
much improved" or "much improved" compared to 2/26 (8%) of
controls (p = 0.0471); 24/30 (80%) in the treatment group improved compared to
10/26 (38%) of controls (p = 0.0024). Mean parental CGI scores significantly
improved in the treatment group compared to controls in overall functioning (p
= 0.0336), receptive language (p = 0.0168), and eye contact (p = 0.0322). On
the ABC, significant improvements were observed in the treatment group in total
score, irritability, stereotypy, hyperactivity, and speech (p < 0.03 for
each), but not in the control group. In the treatment group compared to the
control group, mean changes on the ABC total score and subscales were similar
except a greater number of children improved in irritability (p = 0.0311). On
the ATEC, sensory/cognitive awareness significantly improved (p = 0.0367) in
the treatment group compared to the control group. Post-hoc analysis indicated
that children over age 5 and children with lower initial autism severity had
the most robust improvements. Hyperbaric treatment was safe and well-tolerated.
CONCLUSION: Children with autism who received hyperbaric treatment at 1.3 atm
and 24% oxygen for 40 hourly sessions had significant improvements in overall
functioning, receptive language, social interaction, eye contact, and
sensory/cognitive awareness compared to children who received slightly
pressurized room air. TRIAL REGISTRATION: clinicaltrials.gov NCT00335790.